P3, N=812, Recruiting, Hoffmann-La Roche | Trial completion date: Sep 2032 --> Dec 2030 | Trial primary completion date: Aug 2026 --> Mar 2027

P2, N=120, Active, not recruiting, University of California, Irvine | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

Treatment included IT delivery of cDC1, 6 times weekly, followed by paclitaxel, 80 mg/m2, intravenously, 12 times weekly...In this nonrandomized clinical trial, the addition of IT cDC1 and trastuzumab/pertuzumab before neoadjuvant chemotherapy was well tolerated with manageable adverse effects. Based on safety and immunogenicity, DL2 was selected for the phase 2 dose. ClinicalTrials.gov Identifier: NCT05325632.

P=N/A, N=156, Not yet recruiting, Yunnan Cancer Hospital

P2, N=139, Terminated, Jules Bordet Institute | N=1065 --> 139 | Trial completion date: Mar 2029 --> Nov 2024 | Suspended --> Terminated | Trial primary completion date: Jun 2027 --> Nov 2024; Serious concerns on the slow recruitment of the study that impacts the robustness of the scientific rationale and the study financial provision. It aims to assess carefully the situation and to evaluate the potential solutions to overcome the issues.

In patients with pCR who responded to chemotherapy and dual HER2 blockade (TP), the 3-year RFS and brain metastasis-free survival did not differ according to the type of adjuvant anti-HER2 therapy.

These findings might suggest a potential advantage of nab-paclitaxel combined with trastuzumab and pertuzumab compared with the standard regimen in neoadjuvant therapy for patients with HER2-positive early breast cancer, suggesting that this new combination might establish a new standard for neoadjuvant treatment in this patient population.

P3, N=230, Recruiting, Hoffmann-La Roche | Trial completion date: Oct 2028 --> Jan 2028 | Trial primary completion date: Oct 2028 --> Oct 2026

P2, N=74, Not yet recruiting, University of Chicago | Initiation date: Jul 2024 --> Jan 2025

P2, N=45, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

This initiative demonstrated the ability to rapidly and effectively transition >95% of eligible breast cancer patients from separate IV trastuzumab and pertuzumab to a fixed combined SC formulation. Patient benefits included shorter administration appointments and a less invasive form of treatment, whereas healthcare system benefits included substantial savings in aseptic preparation time and chair time, and a meaningful increase in clinic capacity. The reported treatment-switch process provides a model that can be adopted by other centres wishing to implement similar treatment switches.

SC formulations of anti-HER2 monoclonal antibodies offer several advantages over IV counterparts, including shorter administration time, less need for IV access, and better resource utilization for treatment facilities. This review summarizes the clinical data supporting the use of SC trastuzumab and PH FDC SC injection in treating early-stage and metastatic HER2-positive breast cancer and highlights the benefits of SC injection compared to the IV formulations.

A low baseline SII is associated with better survival outcomes among HER2-positive MBC patients receiving trastuzumab-based first-line therapy.

Our study revealed novel functions of DLL4 in cell stemness and immune infiltration, including NET formation and T cell exclusion, which collectively contributed to THP neoadjuvant therapy resistance in HER2+ BC. Furthermore, we provided a CAR-T-based therapy to sensitize the THP neoadjuvant therapy.

P3, N=96, Terminated, Hoffmann-La Roche | Completed --> Terminated; Due to low enrollment, the Sponsor decided to prematurely terminate the study

The economic viability of dual HER2-targeted therapy was most pronounced in patients with node-positive high-risk early breast cancer. This study highlights the potential of dual HER2-targeted therapy as a cost-effective addition for these cases.

In this regard, we also found that the savings produced from switching from the traditional intravenous treatment to the subcutaneous one would allow EsSalud to afford full annual costs of 2 additional treatments, but without increasing their budget. This would cover 7% of the gap of 29 patients who do not have access to full treatment.

P2, N=220, Active, not recruiting, West German Study Group | Recruiting --> Active, not recruiting | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Aug 2015 --> Jan 2025

P2, N=402, Recruiting, West German Study Group | Not yet recruiting --> Recruiting

P2, N=86, Completed, UNICANCER | Active, not recruiting --> Completed

In this study, we analyzed the intrinsic subtype of HR positive, HER2 positive breast cancer based on prediction analysis of microarray 50 (PAM50) and Breast Cancer 360 panel (nanostring) between durable and poor responder in first-line docetaxel + trastuzumab + pertuzumab (THP) treated patients. Conclusions Other than HER2 pathway, ER pathway and inflammatory signal may influence the tumor response of HR(+), HER2 (+) breast cancer. Further clinical trials should be designed based not only on HER2 status, ER status and other molecular subtypes should be considered to maximize the clinical benefit.

Tumors with Ki67 <30 were associated with a lower rate of pCR after completing neoadjuvant treatment. Ki67 was kept as an independent predictor for pCR regardless of the use of neoadjuvant antracycline or trastuzumab plus pertuzumab, and HER2 score as evaluated by IHC. In the future, PAM 50 or another multigenic test may better fit these patients into different prognostic subgroups and help to de-escalate treatment.

Patients received neoadjuvant treatment with taxanes and subcutaneous fixed dose combination pertuzumab and trastuzumab (P+T) for a total duration of 12 weeks followed by surgery. Adjuvant treatment was determined according to response at surgery: patients with a pathologic complete response (pCR, defined as pT0/Tis pN0) received adjuvant P+T for additional 14 cycles, while patients with residual disease received adjuvant trastuzumab emtansine (T-DM1) for 14 cycles... Neoadjuvant treatment with an anthracycline-free regimen in patients with HER2-positive, hormone receptor negative, node-negative early breast cancer resulted in a high rate of pCR. The majority of patients achieving pCR had the HER2-enriched PAM50 subtype.

For HER2+ aBC (HER2 IHC 3+ or 2+/ISH+), 1L standard of care includes unconjugated HER2 antibodies trastuzumab and pertuzumab (HP) in combination with chemotherapy...For some targeted therapies, including MET inhibitor capmatinib, the magnitude of genomic copy number (CN) gains predict benefit... In a cohort of real-world aBC pts treated with HER2 antibody therapies, HER2 CN ratio was significantly associated with clinical outcomes. For unconjugated antibodies, pts with a HER2 CN ratio of <5 had significantly shorter TTD, PFS and OS. Future work should explore whether these pts may benefit from therapy escalation (e.g.

72 of 84 patients were treated with traditional neoadjuvant chemotherapy plus trastuzumab meanwhile 12 of 84 received neoadjuvant chemotherapy plus trastuzumab and pertuzumab. We would like to acknowledge the contribution of Multispecialistic Biobank Research Core Facilty G-STeP, Fondazione Policlinico Universitario "A. Gemelli" IRCCS (Biobank-FPG) who provided the bioresources.

While immune markers such as TILs and PD-L1 scores are not typically measured in HER2-positive breast cancers, this data opens up the possibility of rationally leveraging targeted therapies in this subset of immune and HER2-sensitive breast cancers, thus potentially avoiding chemotherapy in the future for this biologically selected group. This regimen holds promise as an effective, relatively non-toxic, and biologically-driven alternative to standard chemotherapy for patients with HER2- enriched subset of early breast cancer.

ESMO Breast 2024) and following T-DM1 monotherapy in the second-line setting or beyond (Brasó-Maristany et al. The HER2DX ERBB2 mRNA score is strongly associated with long-term survival outcomes in metastatic HER2+ breast cancer treated with first-line THP. Notably, HER2DX identified patients with ERBB2-low disease, as the subgroup with the poorest outcomes in both PFS and OS. Further analyses will be presented at the conference.

Consequently, we determined that the patient presented with a condition similar to immune thrombocytopenic purpura (ITP) and selected a treatment approach consisting of eltrombopag, a thrombopoietin receptor agonist. Although uncommon, anti-HER2 antibodies can cause severe thrombocytopenia. Furthermore, if thrombocytopenia persists after treatment discontinuation and the administration of corticosteroids, exploring treatment options aligned with managing ITP is essential.

In those with RD, 36% lost HER2(+) status; IDFS events appeared similar in those with HER2(+) RD versus those with HER2(-) RD. The BM events seen in those with RD and pCR highlights the need for more effective therapy in NAST and adjuvant setting to minimize BM risk.

Dual human epidermal growth factor receptor 2(HER2)blockade with trastuzumab(H)and pertuzumab(P)combined with docetaxel and carboplatin(TCb)is a standard neoadjuvant therapy for HER2-positive breast cancer patients. 4 cycles of T-DM1+P). Simultaneous administration of H and P enables a reduced administration time, which would benefit both patients and healthcare providers.

Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved an adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling.

Undifferentiated thyroid cancer (ATC) is highly malignant and does not respond well to sorafenib (SRF) treatment owing to the lack of specificity of SRF targeting...Therefore, we developed a pH-responsive nano-targeted drug delivery systems using human serum albumin (HSA) as a carrier to generate manganese dioxide (MnO2)@HSA nanoparticles (NPs), then encapsulated SRF and the fluorescent dye indocyanine green (ICG) and finally modifyed the targeting antibody pertuzumab in the outer layer of the nano complexes, resulting in SRF/ICG/MnO2@HSA-pertuzumab (HISMP) NPs...In vivo MR/NIRF imaging experiments confirmed that the HISMP NPs specifically aggregated at tumor sites and have good in vivo MR/NIRF imaging ability and effective anti-tumor activity. The nano-delivery system is expected to provide a theoretical foundation for the efficient ATC diagnosis and therapy.

The patient received neoadjuvant chemotherapy with epirubicin and cyclophosphamide, followed by docetaxel, trastuzumab, and pertuzumab...A liver biopsy following treatment with trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-Dxd) revealed HER2-negative status. Cyclin-dependent kinase (CDK) 4/6 inhibitor combination endocrine therapy has been continued for 16 months to date while maintaining tumor shrinkage. It is essential to perform a rebiopsy during treatment to optimize therapy based on the subtype.

P2, N=53, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting

Our results are in line with the CLEOPATRA and EMILIA studies, but long-term responders in the arm A may have impacted our results. The absence of difference in term of PFS in first metastatic line may be explained by a selection bias, as patients in the arm A potentially have more aggressive forms.

HER2-targeted drugs such as HerceptinTM (trastuzumab), PERJETA® (pertuzumab) and KADCYLA® (adotrastuzumab emtansine) are beneficial for HER2-positive breast cancer patients who will inhibit cell signaling pathways. If the FISH results are negative for HER2 IHC equivocal, this is considered HER2-Low. Significantly, Enhertu has shown a promising objective response in HER2-Low breast cancer patients.

P2, N=20, Suspended, University of Rochester | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Jun 2026

P3, N=516, Active, not recruiting, Helsinki University Central Hospital | Trial primary completion date: Dec 2021 --> Jul 2025

P2, N=23, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2024 --> Nov 2024

Targeted therapies like trastuzumab deruxtecan (T-DXd), trastuzumab, pertuzumab, and T-DM1 have revolutionized HER2-positive metastatic breast cancer (MBC) treatment. Personalized approaches have boosted HER2-positive MBC outcomes, and ongoing research is crucial to uncover new treatments and biomarkers, potentially elevating long-term response rates and prognoses. This may aid in providing new direction to breast cancer clinics.

Managing Li-Fraumeni syndrome (LFS) and its associated cancers, particularly in young patients, necessitates a comprehensive and multidisciplinary approach. Early genetic testing for TP53 mutations is crucial in identifying LFS, enabling personalized treatment plans and proactive surveillance strategies.

In November 2013, for neck nodal progression, seven cycles of chemotherapy (cisplatin and epirubicin) associated with a humanized monoclonal antibody-targeting HER 2 therapy (trastuzumab and pertuzumab) were performed, with a marked response rate. In primary ductal adenocarcinoma of the lacrimal gland, early diagnosis and multimodal treatments could be crucial, considering its often aggressive tendency. Considering the lack of treatment guidelines, case report recording can be useful in patient management.